Lessons from global survey on Lp(a) levels in CHD

This summary is based on the presentation of Kausik Ray, MD (London, UK) at the ESC Congress 2024 - A global perspective of Lp(a) levels in patients with coronary heart disease - Implications for risk factor control & future trials from the INTERASPIRE Study.

Introduction and methods

Lp(a) is a lipoprotein composed of apo(a), which is covalently bound to apoB-100–containing LDL-like particles. Higher Lp(a) levels increase the lifetime risk of ASCVD. As Lp(a) levels are predominantly genetically determined, it is important to control all other risk factors.

An international group of researchers therefore set out to answer several questions, including to what extent do Lp(a) levels vary in patients with recent CHD globally, can gaps in lifestyle and risk factor management be mitigated to offset high Lp(a)-related risk, and what is the relationship of Lp(a) with LDL-c, non–HDL-c, and apoB.

For this purpose, they collected data from the INTERASPIRE survey, an international study in patients recently diagnosed with CHD designed to determine whether guideline standards for secondary prevention and cardiac rehabilitation are being followed accurately. This study was an expansion of the EUROASPIRE (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) program and included 14 countries in all 6 WHO regions. Participants were invited to a standardized interview and examination; Lp(a) levels were available for 13 countries. Importantly, physicians were unaware of their patients’ Lp(a) levels.

Main results

• There were 3928 CHD patients, who had a median Lp(a) level of 32 nmol/L (IQR: 11–89).
• The Lp(a) distribution varied between WHO regions and between countries within each region.
• The cumulative distribution of Lp(a) levels showed 19.6% of the participants had Lp(a) ≥115 nmol/L, which is the typical threshold considered to increase ASCVD risk. Of note, this threshold is lower than the cutoff values used in recent RCTs on various Lp(a)-lowering treatments (range: 150–200 nmol/L).
• When a fixed Lp(a) threshold was applied, the proportion of patients potentially eligible for Lp(a)-lowering trials varied between countries. • Lp(a) levels were higher in women, patients with renal impairment, and patients with peripheral artery disease and lower in patients receiving PCSK9 inhibitor treatment.
• In 1.8% of the patients with Lp(a) ≥115 nmol/L, all manageable lifestyle and risk factors, such as smoking, hypertension, and increased BMI, were controlled.
• Even in patients with Lp(a) levels in the highest deciles, LDL-c, non–HDL-c, and apoB levels were not significantly different from those in the lower Lp(a) deciles.

Conclusion

In the INTERASPIRE survey among patients with recent CHD, median Lp(a) levels (32 nmol/L) were much lower than the threshold considered to increase ASCVD risk (115 nmol/L). The potential eligibility for Lp(a)-lowering trials depended on the Lp(a) cutoff value used and varied by country. There was a clear gap in lifestyle and risk factor management, with only 2% of the patients with Lp(a) ≥115 nmol/L being adequately managed. As other lipid parameters are not indicative of elevated Lp(a) levels, Dr. Ray stressed the importance of measuring Lp(a) directly.

- Our reporting is based on the information provided at the ESC Congress 2024 -

The main results of the INTERASPIRE study were simultaneously published in Eur Heart J.